The principal objective of this research proposal is to prove the feasibility of replacing an irreparably damaged heart with a total artificial heart (TAH). Recent progress has led to extended survival times of experimental animals (over 200 days), supported entirely by a pneumatically powered polyurethane artificial heart, which in turn has presented several new questions which must be answered before human application of a TAH may be contemplated. We propose to deal with specific aims directed at materials (durability and biocompatibility), cardiodynamics and hemodynamics, device-tissue interface, device-blood interface, device-entire-host; and surgical and medical procedures for implanting and maintaining a TAH through a series of in vitro and in vivo experiments using the Jarvik-5 and Jarvik-7 Artificial Heart. A number of specific protocols have been designed to address 18 hypotheses, identified to be important in the evolvement of the TAH system to clinical realization. These protocols center around three primary groups of experiments: 1) instrumental control animals; 2) lightly monitored; and 3) heavily instrumented monitored and studied TAH calves, a subgrouping of which will be sacrificed at predetermined times (two, three and four months). These investigations incorporate standard sophisticated procedures for evaluating a complex experimental TAH animal model, by focusing on specific areas. These include: cardiodynamics and hemodynamics at rest and exercise as influenced by cardiovascular agents; blood chemistry and hematologic parameters; blood coagulation kinetics and blood volume determinations; material tissue interactions: fibrosis; and effects of body fluids and blood constituents absorbed onto and imbibed into the polymers used for fabricating the device. The atria, the important junction between the device and the recipient, will be evaluated by function and contribution to TAH performance and pathology.